1. Improving outcomes in AKI and CRRT: Does Quality matter?
Timothy E. Bunchman
Professor and Director
Pediatric Nephrology & Transplantation

2. Overview
What has occurred to improve the diagnosis and outcome in AKI in children
What has occurred to improve the use of CRRT in children

3. How do you diagnosis AKI?
Severity of illness score?
Biomarkers?
FO?
Uremia?

4. Historically
AKI diagnosis was synominous with the need for renal replacement therapy
Uremia, hyperkalemia, metabolic acidosis
In 2000 ADQI occurred and began to quantitate and measure markers of AKI

5. RIFLE Criteria

6. Modified Pediatric RIFLE
Goldstein et al , KI 2007
Now validated in 3 additional Pediatric Studies

7. LIMITATIONS OF AKI CLASSIFICATION CRITERIA
pRIFLE
AKIN
KDIGO
inconsistency in application
urinary output criteria often excluded → loss of additional cases
exclusion of patients with elevated initial SCr
UO and sCr are late markers
Biomarkers…

8. AKI diagnosis: pRIFLE 51%, AKIN 37.3%, KDIGO 40.3%

9. AKI = 50% or greater increase in serum creatinine from baseline
Urine NGAL as an Early AKI Biomarker after Cardiopulmonary Bypass
AKI = 50% or greater increase in serum creatinine from baseline
Mishra et al, Lancet 2005, 365:

10. Dialysis Dose and Outcome Ronco et al. Lancet 2000; 351: 26-30
425 patients
Endpoint = survival 15 days after D/C HF
146 UF rate 20ml/kg/hr
survival significantly lower
in this group compared
to the others
139 UF rate 35ml/kg/hr
p=0.0007
140 UF rate 45ml/kg/hr
p=0.0013
Conclusions:
Minimum UF rates should be ~ 35 ml/kg/hr
Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

11. 26.9% of all patients 11.6% of all patients 3.5% of all patients
AWARE Investigators– submitted

12. So what! The diagnosis of AKI and the need for RRT are discreptent But
If AKI at risk is 25% of all PICU admissions then attention to detail of nephrotoxins and fluid over load are needed to avoid the worsening of AKI

13. SPECIAL FIBERS AND FILTERS HAVE BEEN DESIGNED FOR SPECIAL CONDITIONS AND PATIENTS
Minifilters
Ronco C, et al Treatment of acute renal failure in newborns by Continuous Arterio-Venous Hemofiltration. Kidney International, 1984

14. 1980s
Following Ronco’s paper little was published except for a descriptive paper by Leone et al describing CAVH in children
Early experience with continuous arteriovenous hemofiltration in critically ill pediatric patients. Crit Care Med Dec;14(12):
Neonatal work by Zobel
Continuous arteriovenous hemofiltration in premature infants. Crit Care Med Jun;17(6):534-6.

15. 1990s Equipment during this era was “adaptive”
Solutions for convection or diffusion was pharmacy made or lactate based
Latter part of 1990s industry began to market machines that did not take momentum until turn of the decade

16. 1990s
Important work on Access was presented by John Gardner RN describing the MAHURKAR™ Catheter that is now marked by Covidien
“how to do it papers”
Continuous arterial-venous diahemofiltration and continuous veno-venous diahemofiltration in infants and children. Pediatr Nephrol Feb;8(1):
Continuous venovenous hemodiafiltration in infants and children. Am J Kidney Dis Jan;25(1):17-21.
Out come paper by Smoyer et al on
Determinants of survival in pediatric continuous hemofiltration. J Am Soc Neph 1995 Nov;6(5):
Comparison paper on CAVH vs CVVH by our group in Am J Kid Dis 1995
Maxvold and colleagues began comparison of modalities
Management of acute renal failure in the pediatric patient: hemofiltration versus hemodialysis. Am J Kidney Dis Nov;30(5 Suppl 4):S84-8.

17. 1990s Evaluation of PICU needs and RRT beyond AKI began
Parekh RS et al
Dialysis support in the pediatric intensive care unit. Adv Renal Replac Therapy 1996 Oct;3(4):
Quigley and associates on use of HD and hemofiltration in TLS
Hyperphosphatemia in tumor lysis syndrome: the role of hemodialysis and continuous veno-venous hemofiltration. Peds Nephrol 1994, 8: 351-3

18. 2000s This era exploded with advancements in Equipment
FDA approval of bicarbonate based Solutions
Nutrition in AKI/CRRT
Avoidance of complications
Anticoagulation protocols

19. 2000s
Gambro and B Braun (and soon to follow Baxter) came out with machines with commonality of warmer, accurate fluid control as well as blood flow and solutions controllers

20. 2000s
FDA approval of bicarbonate based Solutions by Dialysis Solution Inc and Walter O’Rourke
Pediatric hemofiltration: Normocarb dialysate solution with citrate anticoagulation. Pediatr Nephrol :150-4
Maxvold et al described Nutrition needs and losses in AKI/CRRT
Amino acid loss and nitrogen balance in critically ill children with acute renal failure: a prospective comparison between classic hemofiltration and hemofiltration with dialysis. Crit Care Med :1161-5

21. 2000s Anticoagulation Protocols
Pediatric acute renal failure: outcome by modality and disease. Pediatr Nephrol 2001, 16:
Pediatric convective hemofiltration: Normocarb replacement fluid and citrate anticoagulation. Am J Kid Dis :
Brophy et al
Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). NDT :

22. Circuit survival censored for
Seven ppCRRT centers
138 patients/442 circuits
3 centers: hepACG only
2 centers: citACG only
2 centers: switched from hepACG to citACG
HepACG = 230 circuits
CitACG= 158 circuits
NoACG = 54 circuits
Circuit survival censored for
Scheduled change
Unrelated patient issue
Death/witdrawal of support
Regain renal function/switch to intermittent HD

24. Heparin vs citrate prospective study Zaoral et al, Pediatric Critical Care Medicine. 17(9):e399–e405, SEP 2016
“ We showed in our study that citrate provided significantly longer circuit lifetimes than heparin for continuous venovenous hemodialysis in children. Citrate was superior to heparin for the transfusion requirements. Citrate was feasible and safe in children and infants”.

25. Convective Clearance CVVH Convective clearance Replacement Solutions
Physiologic sterile solution that is either infused pre filter (NA) or post filter (outside of NA) that infused at a set rate (Qr)

26. Diffusive Clearance CVVHD/HD/PD Diffusive clearance Dialysate
Physiologic sterile solution that is infused countercurrent to the blood flow rate (Qd)

27. Convective and Diffusive Clearance (? Confusion)
CVVHDF/CAVHDF
Convective clearance
Replacement Solutions
Diffusive clearance
Dialysis solution

28. Stem Cell Transplant: ppCRRT
51 patients in ppCRRT with SCT
Mean %FO = %.
45% survival
Convection: 17/29 survived (59%)
Diffusion: 6/22 (27%), p<0.05
Survival lower in MODS and ventilated patients
Flores FX et al: Pediatr Nephrol Apr;23(4):625-30

29. Prospective Pediatric Study
40 patients with Sepsis/ARF at 4 ppCRRT centers
Randomized crossover design
24 hours of CVVH or CVVHD, then crossover
2500 ml/hr/1.73m2 clearance
Dialysis/Replacement fluid with [HC03]=35mmol/l
Citrate ACG
Serum collection at 0,1, 24, 25 and 48 hours
TNF-alpha
IL-1 beta
IL-6, IL- 8, IL-10, IL-18
Six hours of effluent for CK’s for clearance estimation

30. ppCRRT Sepsis Study 10 patients enrolled to date PELOD
6 male, 4 female
Mean age years
Mean weight kg
PELOD
Mean =
Median = 22 (range 11-42)

31. ppCRRT [Cytokine] % Change: Convection vs. Diffusion
TNF-alpha
0.08
IL-1 beta
0.46
IL-6
0.21
IL-8
0.018
IL-10
0.007
IL-18
0.002
PELOD
0.26

32. Leaders in the Field
Stu Goldstein began the ppCRRT and now the ppAKI study groups that have balanced research, QI with advancements

33. Has RRT improved out come?
All modalities of RRT have changed from adaptive to newer products for children of all ages
In the 90’s reports of 45 % survival rates have been replaced by current 65% survival rates in sepsis AKI

34. Has RRT improved out come?
In the 90’s reports of 17 % survival rates have been replaced by current 53% survival rates in liver AKI as reported by Deep and Colleagues

35. Conclusion
QI and Research have improved the diagnosis of AKI and the use of RRT
Since the beginning of this time, patients have more co-morbidities and are more complicated

36. Future Areas primed for prospective and future research/QI include
Optimal med dosing
Optimal nutrition delivery
Non dialytic options of treatment of AKI
Science around starting and stopping RRT